ArticleFrontiers in immunology2026
Interaction between HLA-B leader peptide variants and cytomegalovirus serostatus is associated with early T cell-mediated rejection in kidney transplantation.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Mismatches between mature recipient and donor HLA proteins can trigger alloreactivity upon transplantation. Recent studies suggest that also the leader peptide of HLA class I alleles may affect the transplantation outcome. In this retrospective study, we examined the association between the HLA-B leader -21 methionine (M)/threonine (T) dimorphism and T cell-mediated rejection (TCMR) early after kidney transplantation. In a hypothesis-generating cohort of 351 transplants, -21MM recipients experienced significantly increased odds of early TCMR within the first 90 days post-transplantation compared to -21TT recipients (odds ratio (OR) 4.57, 95% confidence interval (CI) 1.87-10.95, p<0.001), irrespective of the donor's HLA-B leader peptide. This association was most prominent among CMV-seropositive recipients (OR 10.91, 95% CI 3.24-39.24, p<0.001). In an independent cohort (n=936), -21MM CMV-seropositive recipients seemed to be at increased odds of early TCMR. In parallel, among CMV-seropositive recipients, -21MT recipients had a significantly increased likelihood of developing early TCMR (OR 2.74, 95% 1.08-7.88, p=0.04). Combined, CMV-seropositivity in the presence of a -21M leader peptide associated with early TCMR with an OR of 2.95 (95% CI 1.49-5.86, p=0.002). In both cohorts, the effect of the -21M leader peptide was most prominent among recipients mismatched for an HLA-A/-C leader peptide. Conclusively, this study suggests that recipients with an HLA-B -21M leader peptide have increased odds of early TCMR, which is further influenced by the recipient's CMV serostatus. While the underlying mechanism remains speculative, these findings indicate that the HLA-B leader peptide of the recipient may affect immune regulation and early TCMR after kidney transplantation.
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